ReferenceID 2777
Upregulation of CD86 and IL-12 by rhododendrol in THP-1 cells cocultured with melanocytes through ROS and ATP
J Dermatol Sci
Background: The tyrosinase inhibitor rhododendrol (RD), used as a skin whitening agent, reportedly has the potential to induce leukoderma. Objective: Although an immune response toward melanocytes was demonstrated to be
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Record Fields
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- Reference Id
- 2777
- Evidence Id
- 19367
- Core Evidence Id
- 19367
- Source Reference Id
- 5550
- Herb2 Reference Id
- HBREF006347
- Subject Paper Key
- HBIN042253_36610941
- Pubmed Id
- 36610941
- Doi
- 10.1016/j.jdermsci.2022.12.012
- Paper Title
- Upregulation of CD86 and IL-12 by rhododendrol in THP-1 cells cocultured with melanocytes through ROS and ATP
- Paper Abstract
- Background: The tyrosinase inhibitor rhododendrol (RD), used as a skin whitening agent, reportedly has the potential to induce leukoderma. Objective: Although an immune response toward melanocytes was demonstrated to be involved in leukoderma, the molecular mechanism is not fully understood. Methods: We hypothesized that if RD is a pro-hapten and tyrosinase-oxidized RD metabolites are melanocyte-specific sensitizers, the sensitizing process could be reproduced by the human cell line activation test (h-CLAT) cocultured with melanocytes (h-CLATw/M) composed of human DC THP-1 cells and melanoma SK-MEL-37 cells. Cell surface expression, ROS generation and ATP release, mRNA expression, and the effects of several inhibitors were examined. Results: When RD was added to the h-CLATw/M, the expression of cell-surface CD86 and IL-12 mRNA was greatly enhanced in THP-1 cells compared with those in the h-CLAT. The rapid death of melanoma cells was induced, with ROS generation and ATP release subsequently being greatly enhanced, resulting in the cooperative upregulation of CD86 and IL-12. Consistent with those observations, an ROS inhibitor, ATP receptor P2X7 antagonist, or PERK inhibitor antagonized the upregulation. CD86 upregulation was similarly observed with another leukoderma-inducible tyrosinase inhibitor, raspberry ketone, but not with the leukoderma noninducible skin-whitening agents ascorbic acid and tranexamic acid. Conclusion: RD is a pro-hapten sensitizer dependent on tyrosinase that induces ROS generation and ATP release from melanocytes for CD86 and IL-12 upregulation in DCs, possibly leading to the generation of tyrosinase-specific cytotoxic T lymphocytes. The coculture system h-CLATw/M may be useful for predicting the sensitizing potential to induce leukoderma.
- Journal
- J Dermatol Sci
- Publish Year
- 2023
- Experiment Subject
- human; h-clat; h-clatw/m; human dc thp-1 cells; melanoma sk-mel-37 cells; thp-1 cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Melanoma; Leukoderma
- Paper Title Cn
- Paper Title En
- Upregulation of CD86 and IL-12 by rhododendrol in THP-1 cells cocultured with melanocytes through ROS and ATP
- Bilingual Status
- semi_complete